The objective of the proposed studies is to describe the electrophysiologic changes which occur in cardiac cells during the development of heart failure, ventricular hypertension and myocardial ischemia, and to delineate the action of old and new drugs which limit the onset, progress and severity of these diseases. Previously, our laboratory recognized and characterized alterations in the electrical activity and responsiveness of cardiac cells in experimental pressure overload-induced hypertrophy and cardiac failure and myocardial infarction. We now expand these areas of interest to encompass analysis of the electrophysiologic consequences of myocardial infarction in the setting of chronic ventricular systolic hypertension. We propose 5 further projects concerning these subjects as follows: 1. to examine whether potent ionophores will prevent or modify electromechanical responses to chronic ventricular pressure overload; 2. to describe whatever changes occur in myocardial ionic currents (and potentials) during the development of hypertrophy and cardiac failure and modification of these currents by various drugs; 3. to determine whether excitation-contraction (or contracture) coupling is altered during the progression from hypertrophy to failure; 4. to elucidate both short- and long-term cellular abnormalities and cardiac arrhythmias which arise from acute myocardial infarction in the hypertrophied ventricle; and 5. to estimate the relative contributions of reentrant and automatic mechanisms to the genesis of these arrhythmias. The actions of antiarrhythmic drugs and specific ionic channel blockers on the abnormal myocardial cellular potentials, automaticity and conduction during these disease states will be analyzed and contrasted with their effects on normal tissue. These data should contribute to our understanding of progessive cardiomyopathies and potentially lethal arrhythmias in humans and their therapy.